Intraosseous growth of human prostate cancer in implanted adult human bone: Relationship of prostate cancer cells to osteoclasts in osteoblastic metastatic lesions

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Abstract
BACKGROUND More than 80% of patients with advanced prostate cancer have skeletal involvement, but the biology of bone metastasis is poorly understood. This study investigated the in vivo formation and progression of bone metastases under conditions that resembled the human bone environment as closely as possible. METHODS Adult human bone fragments were implanted subcutaneously into 120 male NOD/SCID mice. Four weeks later, 1 × 107 LNCaP prostate cancer cells or phosphate‐buffered saline were injected intravenously into 80 or 40 mice, respectively. The implanted bone fragments were removed from 20 to 10 mice in each group at 2, 4, 6, and 8 weeks after injection. RESULTS LNCaP colonized the bone marrow blood vessels within 2 weeks, and then gradually expanded into the entire medullary cavity. An osteoblastic response often occurred at the edges of metastatic foci (intertrabecular bone metaplasia). In addition, new bone formation was observed adjacent to mature lamellar bone (appositional bone formation). These two processes appeared to occur through different mechanisms, but might similarly cause osteosclerosis. Osteoclasts showed a marked increase in numbers at sites of early tumor invasion, whereas few osteoclasts were observed at sites where tumor invasion was complete. CONCLUSIONS The predominance of osteoblastic change with resorption may lead to bone remodeling in metastatic lesions, and osteoclasts may play an important role in bone metastasis from prostate cancer.

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